Does a regular expression exist for enzymatic cleavage?

Question

Does a regular expression exist for (theoretical) tryptic cleavage of protein sequences? The cleavage rule for trypsin is: after R or K, but not before P.

Example:

Cleavage of the sequence VGTKCCTKPESERMPCTEDYLSLILNR should result in these 3 sequences (peptides):

 VGTK
 CCTKPESER
 MPCTEDYLSLILNR

Note that there is no cleavage after K in the second peptide (because P comes after K).

In Perl (it could just as well have been in C#, Python or Ruby):

  my $seq = 'VGTRCCTKPESERMPCTEDYLSLILNR';
  my @peptides = split /someRegularExpression/, $seq;

I have used this work-around (where a cut marker, =, is first inserted in the sequence and removed again if P is immediately after the cut maker):

  my $seq      = 'VGTRCCTKPESERMPCTEDYLSLILNR';
  $seq         =~ s/([RK])/$1=/g; #Main cut rule.
  $seq         =~ s/=P/P/g;       #The exception.
  my @peptides = split( /=/, $seq);

But this requires modification to a string that can potentially be very long and there can be millions of sequences. Is there a way where a regular expression can be used with split? If yes, what would the regular expression be?

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Test platform: Windows XP 64 bit. ActivePerl 64 bit. From perl -v: v5.10.0 built for MSWin32-x64-multi-thread.

Answer 1

You could use look-around assertions to exclude that cases. Something like this should work:

split(/(?<=[RK](?!P))/, $seq)

Answer 2

You can use lookaheads and lookbehinds to match this stuff while still getting the correct position.

/(?<=[RK])(?!P)/

Should end up splitting on a point after an R or K that is not followed by a P.

Answer 3

In Python you can use the finditer method to return non-overlapping pattern matches including start and span information. You can then store the string offsets instead of rebuilding the string.

Answer 4

You indeed need to use the combination of a positive lookbehind and a negative lookahead. The correct (Perl) syntax is as follows:

my @peptides = split(/(?!P)(?<=[RK])/, $seq);